EP1601698A4 - Physiologically active polypeptide conjugate having prolonged in vivo half-life - Google Patents

Physiologically active polypeptide conjugate having prolonged in vivo half-life

Info

Publication number
EP1601698A4
EP1601698A4 EP04720540A EP04720540A EP1601698A4 EP 1601698 A4 EP1601698 A4 EP 1601698A4 EP 04720540 A EP04720540 A EP 04720540A EP 04720540 A EP04720540 A EP 04720540A EP 1601698 A4 EP1601698 A4 EP 1601698A4
Authority
EP
European Patent Office
Prior art keywords
life
prolonged
physiologically active
active polypeptide
vivo half
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP04720540A
Other languages
German (de)
French (fr)
Other versions
EP1601698B1 (en
EP1601698A1 (en
Inventor
Young-Min Kim
Dae-Jin Kim
Sung-Min Bae
Chang-Ki Lim
Se-Chang Kwon
Gwan-Sun Lee
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hanmi Pharmaceutical Co Ltd
Hanmi Pharmaceutical Industries Co Ltd
Original Assignee
Hanmi Pharmaceutical Co Ltd
Hanmi Pharmaceutical Industries Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hanmi Pharmaceutical Co Ltd, Hanmi Pharmaceutical Industries Co Ltd filed Critical Hanmi Pharmaceutical Co Ltd
Publication of EP1601698A1 publication Critical patent/EP1601698A1/en
Publication of EP1601698A4 publication Critical patent/EP1601698A4/en
Application granted granted Critical
Publication of EP1601698B1 publication Critical patent/EP1601698B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K19/00Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6883Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

A protein conjugate having a prolonged in vivo half-life of a physiological activity, comprising i) a physiologically active polypeptide, ii) a non-peptidic polymer, and iii) an immunoglobulin, is useful for the development of a polypeptide drug due to the enhanced in vivo stability and prolonged half-life in blood, while reducing the possibility of inducing an immune response.
EP04720540A 2003-03-13 2004-03-13 Physiologically active polypeptide conjugate having prolonged in vivo half-life Expired - Lifetime EP1601698B1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
KR2003015744 2003-03-13
KR20030015744 2003-03-13
KR2003036408 2003-06-05
KR20030036408 2003-06-05
PCT/KR2004/000535 WO2004081053A1 (en) 2003-03-13 2004-03-13 Physiologically active polypeptide conjugate having prolonged in vivo half-life

Publications (3)

Publication Number Publication Date
EP1601698A1 EP1601698A1 (en) 2005-12-07
EP1601698A4 true EP1601698A4 (en) 2006-05-03
EP1601698B1 EP1601698B1 (en) 2009-03-11

Family

ID=36096009

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04720540A Expired - Lifetime EP1601698B1 (en) 2003-03-13 2004-03-13 Physiologically active polypeptide conjugate having prolonged in vivo half-life

Country Status (16)

Country Link
US (2) US20050176108A1 (en)
EP (1) EP1601698B1 (en)
JP (1) JP4481980B2 (en)
KR (1) KR100567902B1 (en)
CN (2) CN1761684A (en)
AT (1) ATE425188T1 (en)
AU (1) AU2004220163B2 (en)
BR (1) BRPI0408331B8 (en)
CA (1) CA2519059C (en)
DE (1) DE602004019887D1 (en)
ES (1) ES2324298T3 (en)
HK (1) HK1177465A1 (en)
IL (1) IL170685A (en)
PT (1) PT1601698E (en)
RU (1) RU2312868C2 (en)
WO (1) WO2004081053A1 (en)

Families Citing this family (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002225681A1 (en) * 2000-11-15 2002-05-27 Globe Immune, Inc. Yeast-dentritic cell vaccines and uses thereof
US7736653B2 (en) 2003-11-13 2010-06-15 Hanmi Pharm. Co., Ltd Pharmaceutical composition comprising an immunoglobulin Fc region as a carrier
US8110665B2 (en) 2003-11-13 2012-02-07 Hanmi Holdings Co., Ltd. Pharmaceutical composition comprising an immunoglobulin FC region as a carrier
EP1765411B2 (en) * 2004-06-30 2017-10-11 Nektar Therapeutics Polymer-factor ix moiety conjugates
HUE033776T2 (en) * 2004-11-12 2018-01-29 Bayer Healthcare Llc Site-directed modification of fviii
BRPI0519562A2 (en) * 2004-12-27 2009-01-27 Baxter Int proteinaceous construct, complex, method for prolonging the in vivo half-life of factor viii (fviii) or a biologically active derivative of the same pharmaceutical composition, and method for forming a proteinaceous construct
KR100754667B1 (en) 2005-04-08 2007-09-03 한미약품 주식회사 Immunoglobulin Fc fragment modified by non-peptide polymer and pharmaceutical composition comprising the same
US20060246523A1 (en) 2005-04-28 2006-11-02 Christopher Bieniarz Antibody conjugates
JP2008545409A (en) * 2005-05-26 2008-12-18 シェーリング コーポレイション Interferon-IgG fusion
US7855279B2 (en) 2005-09-27 2010-12-21 Amunix Operating, Inc. Unstructured recombinant polymers and uses thereof
WO2007049940A1 (en) * 2005-10-27 2007-05-03 Peptron Co., Ltd Bioactive substance-blood protein conjugate and stabilization of a bioactive substance using the same
WO2007062177A2 (en) 2005-11-23 2007-05-31 Ventana Medical Systems, Inc. Molecular conjugate
EP1816201A1 (en) 2006-02-06 2007-08-08 CSL Behring GmbH Modified coagulation factor VIIa with extended half-life
US7645860B2 (en) 2006-03-31 2010-01-12 Baxter Healthcare S.A. Factor VIII polymer conjugates
CA2647314A1 (en) 2006-03-31 2007-11-08 Baxter International Inc. Pegylated factor viii
EP1867660A1 (en) 2006-06-14 2007-12-19 CSL Behring GmbH Proteolytically cleavable fusion protein comprising a blood coagulation factor
US7939632B2 (en) 2006-06-14 2011-05-10 Csl Behring Gmbh Proteolytically cleavable fusion proteins with high molar specific activity
ES2889920T3 (en) 2006-06-14 2022-01-14 Csl Behring Gmbh Proteolytically Cleavable Fusion Proteins with High Molar Specific Activity
EP3231440A1 (en) 2006-12-22 2017-10-18 CSL Behring GmbH Modified coagulation factors with prolonged in vivo half-life
CA2689492A1 (en) * 2007-06-06 2008-12-18 Boehringer Ingelheim International Gmbh Natriuretic fusion proteins
US8742079B2 (en) 2007-08-20 2014-06-03 Protalix Ltd. Saccharide-containing protein conjugates and uses thereof
US20090181037A1 (en) * 2007-11-02 2009-07-16 George Heavner Semi-Synthetic GLP-1 Peptide-FC Fusion Constructs, Methods and Uses
JP5546107B2 (en) * 2008-04-17 2014-07-09 国立大学法人宇都宮大学 RNA virus BmMLV negative silkworm cultured cell line
EP2268807A2 (en) 2008-04-21 2011-01-05 Novo Nordisk A/S Hyperglycosylated human coagulation factor ix
WO2010074082A1 (en) * 2008-12-24 2010-07-01 塩野義製薬株式会社 Modified vasohibin
CN101585864B (en) * 2009-01-05 2011-11-09 天津派格生物技术有限公司 Nitrogen-terminal fixed-point coupling method for colony stimulating factor of column chromatography granulocyte and coupled product
CA2748314C (en) 2009-02-03 2018-10-02 Amunix Operating Inc. Extended recombinant polypeptides and compositions comprising same
EP2408800B1 (en) * 2009-03-20 2016-05-25 Hanmi Science Co., Ltd. Method for preparing a site-specific conjugate of a physiologically active polypeptide
AU2010290131C1 (en) 2009-08-24 2015-12-03 Amunix Operating Inc. Coagulation factor VII compositions and methods of making and using same
US9194011B2 (en) 2009-11-17 2015-11-24 Protalix Ltd. Stabilized alpha-galactosidase and uses thereof
CN102753147B (en) * 2010-01-19 2017-10-31 韩美科学株式会社 The liquid preparation of long-acting erythropoietin conjugate
WO2011090305A2 (en) 2010-01-19 2011-07-28 Hanmi Holdings Co., Ltd Liquid formulations for long-acting g-csf conjugate
WO2011107992A2 (en) * 2010-03-02 2011-09-09 Protalix Ltd. Multimeric forms of therapeutic proteins and uses thereof
KR101337797B1 (en) 2010-07-14 2013-12-06 한미사이언스 주식회사 A liquid formulation of long acting human growth hormone conjugate
KR101382593B1 (en) * 2010-07-21 2014-04-10 한미사이언스 주식회사 Novel long-acting glucagon conjugate and pharmaceutical composition comprising the same for the prevention and treatment of obesity
KR101303388B1 (en) * 2010-10-26 2013-09-03 한미사이언스 주식회사 Liquid formulations of long acting interferon alpha conjugate
AU2011330701A1 (en) * 2010-11-19 2013-07-04 Venus Remedies Limited Novel conjugates for targeted drug delivery
KR101309566B1 (en) * 2010-12-10 2013-09-17 포항공과대학교 산학협력단 Hyaluronic acid-protein conjugate, and preparation method thereof
PL3272861T3 (en) 2011-01-20 2020-07-13 Protalix Ltd. Alpha-galactosidase compositions
CN102309765B (en) * 2011-02-28 2013-10-16 北京韩美药品有限公司 Long-acting anticoagulant polypeptide including immunoglobulin Fc segments as carriers and preparation method of same
RU2502803C2 (en) * 2011-05-20 2013-12-27 Общество с ограниченной ответственностью "Лаборатория медицинской биотехнологии" (ООО "ЛМБТ") PLASMID FOR EXPRESSION IN CELLS OF BACTERIUM BELONGING TO Escherichia CLASS, NON-ACTIVE PREDECESSOR OF DNase I OF HUMAN OR ITS MUTEINS; BACTERIUM BELONGING TO Escherichia CLASS, - PRODUCER OF NON-ACTIVE PREDECESSOR OF RECOMBINANT DNase I OF HUMAN OR ITS MUTEIN; PREDECESSOR OF RECOMBINANT DNase I OF HUMAN OR ITS MUTEIN; METHOD FOR OBTAINING RECOMBINANT DNase I OF HUMAN OR ITS MUTEIN; METHOD FOR OBTAINING CONJUGATES OF POLYETHYLENE GLYCOL AND RECOMBINANT MUTEIN OF HUMAN DNase I, FERMENTATIVE ACTIVE CONJUGATE OF MUTEIN OF RECOMBINANT DNase I OF HUMAN
UA113626C2 (en) 2011-06-02 2017-02-27 A COMPOSITION FOR THE TREATMENT OF DIABETES CONTAINING THE DURABLE INSULIN CON conjugate AND THE DUAL ACTION INSULINOTROPIC PIPIDE
CN102807619B (en) * 2011-06-03 2016-08-03 北京韩美药品有限公司 Containing immunoglobulin Fc segments and the complex of granulocyte-macrophage colony stimutaing factor and pharmaceutical composition thereof
CN102313773B (en) * 2011-07-29 2013-11-20 首都师范大学 Method for identifying quantity of cysteine in protein and application thereof
CA2847837A1 (en) 2011-09-05 2013-03-14 Hanmi Science Co., Ltd. A pharmaceutical composition for treating cancer, comprising interferon alpha conjugate
KR20130049671A (en) 2011-11-04 2013-05-14 한미사이언스 주식회사 Method for preparation of biological active polypeptide conjugate
CN103172745A (en) * 2011-12-21 2013-06-26 北京韩美药品有限公司 Long-acting human endothelium chalone containing immune globulin Fc segment
KR102041412B1 (en) 2011-12-30 2019-11-11 한미사이언스 주식회사 Derivatives of Immunglobulin Fc fragment
EP2623110A1 (en) * 2012-01-31 2013-08-07 CSL Behring GmbH Factor XII inhibitors for the treatment of neurological inflammatory disorders
ES2771208T3 (en) 2012-02-15 2020-07-06 Bioverativ Therapeutics Inc Factor VIII compositions and methods of preparation and use thereof
DK2822577T3 (en) 2012-02-15 2019-04-01 Bioverativ Therapeutics Inc RECOMBINANT FACTOR VIII PROTEINS
AR090281A1 (en) 2012-03-08 2014-10-29 Hanmi Science Co Ltd IMPROVED PROCESS FOR THE PREPARATION OF A PHYSIOLOGICALLY ACTIVE POLYPEPTIDE COMPLEX
US10064951B2 (en) 2012-03-30 2018-09-04 Hanmi Science Co., Ltd. Liquid formulation of highly concentrated long-acting human growth hormone conjugate
CN103235136B (en) * 2012-04-28 2014-12-10 淄博高新区云桥生物技术研究所 Protein medicine three-dimensional conformation antibody array sequence detection method
CN104379598B (en) * 2012-06-05 2017-04-05 Cj医药健康株式会社 Long-acting human growth hormone's albumen of high glycosylation and its production method
AR094821A1 (en) 2012-07-25 2015-09-02 Hanmi Pharm Ind Co Ltd LIQUID FORMULATION OF AN INSULINOTROPIC PEPTIDE CONJUGATE OF PROLONGED ACTION
AR091902A1 (en) 2012-07-25 2015-03-11 Hanmi Pharm Ind Co Ltd LIQUID FORMULATION OF A PROLONGED INSULIN CONJUGATE
US10441665B2 (en) 2012-07-25 2019-10-15 Hanmi Pharm. Co., Ltd. Liquid formulation of long acting insulinotropic peptide conjugate
DK2916819T3 (en) 2012-11-06 2019-10-14 Hanmi Pharm Ind Co Ltd LIQUID FORMULATION OF THE PROTEIN CONJUGATE CONTAINING THE OXYNTOM MODULIN AND AN IMMUNOGLOBULIN FRAGMENT
CN105188750A (en) 2013-03-08 2015-12-23 德国杰特贝林生物制品有限公司 Treatment and prevention of remote ischemia-reperfusion injury
CN103257237B (en) * 2013-05-09 2015-05-20 中国农业大学 In-vitro detection method of allergen in food
AR096890A1 (en) * 2013-07-12 2016-02-03 Hanmi Pharm Ind Co Ltd CONJUGATING FC OF IMMUNOGLOBULINA, THAT MAINTAINS THE UNION AFFINITY OF THE FC FRAGMENT OF THE IMMUNOGLOBULIN TO FCRN
WO2015023891A2 (en) 2013-08-14 2015-02-19 Biogen Idec Ma Inc. Factor viii-xten fusions and uses thereof
US10286078B2 (en) 2013-09-13 2019-05-14 The California Institute For Biomedical Research Modified therapeutic agents and compositions thereof
JP6549104B2 (en) 2013-09-27 2019-07-24 ハンミ ファーマシューティカル カンパニー リミテッド Sustained human growth hormone preparation
CN106456589B (en) 2013-12-18 2020-07-07 斯克利普斯研究所 Modified therapeutic agents, conjugated peptide lipid conjugates and compositions thereof
JP2017505141A (en) * 2014-01-20 2017-02-16 ハンミ ファーマシューティカル カンパニー リミテッド Long-acting insulin and its use
KR102418477B1 (en) 2014-12-30 2022-07-08 한미약품 주식회사 Gluagon Derivatives
BR112017019862A2 (en) * 2015-03-17 2018-05-29 Omniox Inc tumor immunity modulation through protein-mediated O 2 release
WO2017024060A1 (en) 2015-08-03 2017-02-09 Biogen Ma Inc. Factor ix fusion proteins and methods of making and using same
EP3502143A4 (en) 2016-08-19 2020-07-15 Ampsource Biopharma Shanghai Inc. Linker peptide for constructing fusion protein
CN106279437B (en) 2016-08-19 2017-10-31 安源医药科技(上海)有限公司 Hyperglycosylated human coagulation factor VIII fusion proteins and preparation method thereof and purposes
CN106317226B (en) 2016-08-19 2017-09-05 安源医药科技(上海)有限公司 Linker peptide for construction of fusion proteins
RU2656140C2 (en) * 2016-11-14 2018-05-31 Федеральное государственное бюджетное учреждение "Государственный научный центр Институт иммунологии" Федерального медико-биологического агентства России Method for obtaining a hybrid protein containing a fused protein analogue of an interferon gamma conjugated with oligosaccharide
WO2019066603A1 (en) * 2017-09-29 2019-04-04 한미약품 주식회사 Persistent protein conjugate with improved efficiency
CN108164700B (en) * 2017-12-27 2020-05-08 暨南大学 Active oxygen responsive nano carrier for conveying hydrophobic drugs and preparation method thereof
GB201801902D0 (en) 2018-02-06 2018-03-21 Stichting Katholieke Univ Immunomodulatory nanofilaments
KR101974305B1 (en) * 2018-02-14 2019-04-30 한미사이언스 주식회사 Method for preparation of biological active polypeptide conjugate
NZ769677A (en) 2018-05-18 2024-07-05 Bioverativ Therapeutics Inc Methods of treating hemophilia a
US11267858B2 (en) * 2019-05-31 2022-03-08 Spectrum Pharmaceuticals, Inc. Methods of treatment using G-CSF protein complex
JP2021066730A (en) * 2019-10-17 2021-04-30 Jcrファーマ株式会社 Method for producing fusion protein of serum albumin and growth hormone
US11981718B2 (en) 2020-05-27 2024-05-14 Ampsource Biopharma Shanghai Inc. Dual-function protein for lipid and blood glucose regulation
WO2021261712A1 (en) * 2020-06-26 2021-12-30 Sunbio, Inc. Hemoglobin derivative co-conjugated with fatty acid-linked peg and alkoxy peg as a blood substitute

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4232119A (en) * 1977-03-04 1980-11-04 Pharmacia Diagnostics Ab Reagent for use in immunochemical assay methods
US5045312A (en) * 1985-02-18 1991-09-03 Burroughs Wellcome Co. Physiologically active compositions of growth hormone and serum albumin or Ig G
WO1992016221A1 (en) * 1991-03-15 1992-10-01 Synergen, Inc. Pegylation of polypeptides
US5216130A (en) * 1990-05-17 1993-06-01 Albany Medical College Complex for in-vivo target localization
EP0622082A1 (en) * 1992-07-28 1994-11-02 Toray Industries, Inc. Immunocomplex
US5492821A (en) * 1990-11-14 1996-02-20 Cargill, Inc. Stabilized polyacrylic saccharide protein conjugates
US5601825A (en) * 1988-04-01 1997-02-11 Immunomedics, Inc. Therapeutic conjugates of toxins and drugs
US20010028881A1 (en) * 1999-05-28 2001-10-11 Academia Sinica Monoclonal antibody for analysis and clearance of polyethylene glycol and polyethylene glycol-modified molecules
WO2003049684A2 (en) * 2001-12-07 2003-06-19 Centocor, Inc. Pseudo-antibody constructs

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4487325A (en) 1982-07-06 1984-12-11 Owens-Illinois, Inc. Crown closures and containers
WO1992018626A1 (en) * 1991-04-17 1992-10-29 Laboratoire Europeen De Biotechnologie WATER-SOLUBLE POLYPEPTIDES HAVING HIGH AFFINITY FOR INTERFERONS α AND $g(b)
IL124831A0 (en) * 1995-12-27 1999-01-26 Genentech Inc Ob protein derivatives having prolonged half-life
WO2000069913A1 (en) 1999-05-19 2000-11-23 Lexigen Pharmaceuticals Corp. EXPRESSION AND EXPORT OF INTERFERON-ALPHA PROTEINS AS Fc FUSION PROTEINS
PE20010288A1 (en) 1999-07-02 2001-03-07 Hoffmann La Roche ERYTHROPOYETIN DERIVATIVES
ATE407697T1 (en) 1999-07-13 2008-09-15 Bolder Biotechnology Inc ERYTHROPOIETIN IMMUNOLOBULIN FUSION PROTEINS
AU7741000A (en) * 1999-09-30 2001-04-30 Icos Corporation Chitinase immunoglobulin fusion products
EP1539811A4 (en) 2002-09-16 2006-05-24 Elusys Therapeutics Inc Production of bispecific molecules using polyethylene glycol linkers
US7217845B2 (en) 2002-11-25 2007-05-15 Sun Bio, Inc. Bifunctional polyethylene glycol derivatives

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4232119A (en) * 1977-03-04 1980-11-04 Pharmacia Diagnostics Ab Reagent for use in immunochemical assay methods
US5045312A (en) * 1985-02-18 1991-09-03 Burroughs Wellcome Co. Physiologically active compositions of growth hormone and serum albumin or Ig G
US5601825A (en) * 1988-04-01 1997-02-11 Immunomedics, Inc. Therapeutic conjugates of toxins and drugs
US5216130A (en) * 1990-05-17 1993-06-01 Albany Medical College Complex for in-vivo target localization
US5492821A (en) * 1990-11-14 1996-02-20 Cargill, Inc. Stabilized polyacrylic saccharide protein conjugates
WO1992016221A1 (en) * 1991-03-15 1992-10-01 Synergen, Inc. Pegylation of polypeptides
EP0622082A1 (en) * 1992-07-28 1994-11-02 Toray Industries, Inc. Immunocomplex
US20010028881A1 (en) * 1999-05-28 2001-10-11 Academia Sinica Monoclonal antibody for analysis and clearance of polyethylene glycol and polyethylene glycol-modified molecules
WO2003049684A2 (en) * 2001-12-07 2003-06-19 Centocor, Inc. Pseudo-antibody constructs

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
AIMEE GUIDER PAIGE ET AL: "PROLONGED CIRCULATION OF RECOMBINANT HUMAN GRANULOCYTE-COLONY STIMULATING FACTOR BY COVALENT LINKAGE TO ALBUMIN THROUGH A HETEROBIFUNCTIONAL POLYETHYLENE GLYCOL", PHARMACEUTICAL RESEARCH, NEW YORK, NY, US, vol. 12, no. 12, December 1995 (1995-12-01), pages 1883 - 1888, XP009062580, ISSN: 0724-8741 *

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